We propose to remain a Member of the Childhood Liver Disease Research and Education Network (ChiLDReN). As a Charter Member of the Network, our proposal represents a logical extension of the long- standing commitment of our Center to improve the care of children with chronic liver disease through innovative patient-based research. In the previous member of the Network, we worked collaboratively with investigators from other Centers to build a strong infrastructure to conduct patient-based studies on biliary atresia, cholestatic syndromes, mitochondrial hepatopathies and cystic fibrosis. Our key contributions included data submission and analysis of two retrospective studies; leadership in the development, implementation, and completion of the first clinical trial (the steroid trial); high enrollment and retention of subjects into prospective studies; completion of ancillary studies seeking novel molecular phenotypes of biliary atresia; completion of a pilot project on defects in bile acid synthesis; and participation in working groups and committees related to project reviews, writing of manuscripts, and development of core resources. We look forward to significantly contributing to the operation of ChiLDREN through three aims. In Aim 1, we will enroll subjects into prospective ChiLDREN protocols to enable translational science. This will be done by pursuing high enrollment rate of subjects into approved protocols, with the timely collection and submission of data and tissue samples to meet the enrollment goals established by the Network. In Aim 2, we will develop and implement research protocols for clinical trials. We have worked with Network investigators and NIDDK Program Directors to start a new trial for infants with biliary atresia (PRIME trial), and are completing the regulatory requirements to start a trial investigating the efficacy and safety of a small molecule inhibitor of the intestinal sodium-dependent bile acid transporter (IMAGINE-ITCH-INDIGO trial). We are also working in research groups to develop a trial to test a new fat-soluble vitamin preparation to treat vitamin deficiencies in cholestatic children with biliary atresia (CholADEK trial) and the use of glycerol-phenylbutyrate to treat cholestatic children with progressive familial intrahepatic cholestasis (PFIC). And in Aim 3, we will use state-of-the-art molecular techniques in ancillary studies using ChiLDREN data and tissue to discover biomarkers of disease phenotypes and treatment in biliary atresia, and to define genetic mutations in children with mitochondrial hepatopathies. By pursuing the three aims, we will be well positioned to fully execute the new Network aims of pursuing clinical science projects and conducting trials to improve the outcome of children with liver diseases.